The specific aim of this project is to determine concisely whether the pituitary has a function in the regulation of DA receptors in the striatum and N. accumbers in the rat brain. This project has tremendous relevance to the management and prevention of Tardive Dyskinesia (TD), a disorder in humans produced by chronic neuroleptic treatment. I will use an animal model of this disorder and measure the DA receptors, which appear to be involved in the appearance of TD. This will be tested in the animal model of chronic neuroleptic treatment in three experiments. The first experiment will determine if the pituitary is necessary for the maintenance of the DA receptors in the striatum or N. accumbens. Because of the complexity of this subject both male and ovariectomized (ovx) female rats will be used. The DA receptor affinity and density will be measured in the striatum and N. accumbens and the results expressed per mg original wet weight of tissue and per mg of protein in the final homogenate. The groups tested will be intact, sham-operated, and hypophysectomized (Hypox). The second experiment will assess the importance of the pituitary in the increase in the density of these receptors after chronic haloperidol treatment. Haloperidol will be administered at three doses in intact, sham-operated, and Hypox rats for both male and ovx female rats. In the third experiment a neuroleptic that does not cross the blood brain barrier will be used at three doses in the same groups of rats. This will test if only an action on the pituitary can alter the DA receptors in the brain. Preliminary experiments in male rats, comparing intact to Hypox rats, suggest that the pituitary is not necessary for the maintenance of the striatal DA receptors, but does alter the response to haloperidol. This must be more clearly defined in male and female rats because of the possible devasting effect these results would have on the treatment and prevention of TD. If the pituitary is intimately involved with brain DA function, further work will determine if the responsible pituitary hormone is prolactin (current information suggests it might be). Also, in the future, attempts might be made to alter the effect of neuroleptics on prolactin levels and, therefore, hopefully help in the management of the development of TD.